As enantiomers differ only slightly in their physical properties but substantially in their physiological activities it is of fundamental importance for certain applications to obtain the enantiomeric forms separately from one another. This is particularly important in the field of pharmaceuticals. The main goal is to produce compounds which are as enantiomerically pure as possible as an enantiomer can enter into various unforeseeable interactions with other chiral compounds. Nature has developed special chiral catalysts such as enzymes for this purpose which operate enantioselectively with a high degree of activity. By contrast, attempts are made in preparative chemistry to provide stereo selective methods of synthesis which result in only one isomer of high optical purity in a high yield. This can only be achieved in exceptional cases. Another possibility consists of physical methods of separation by means of which the enantiomers produced can be separated.
A frequently used method of enantiomer separation is so called racemate cleaving, i.e. the breaking down of a mixture of equal parts of both enantiomers into the optically active components. One of the most common methods of enantiomer separation is the chemical cleaving of racemic mixtures in which either a racemic acid which is to be separated into the enantiomers if reacted with an optically active base or an optically active acid is reacted with a racemic base, forming a salt. This produces diastereomers which can be separated from one another on the basis of their different solubilities.
Thus, for example, U.S. Pat. No. 4,661,628 describes a method of separating racemic mixtures of α-naphthylpropionic acids by the addition of a β-aminoalcohol, as a result of which the diastereomeric amides formed can be separated by fractional crystallisation and subsequently changed back into the optically active acids by hydrolysis. This separation of the enantiomers is essential as only one of the two isomers has an anti-inflammatory activity. It is internationally known by the name Naproxen.
Also, known physical methods are used for racemate cleaving. Thus, in gas chromatography, thin layer chromatography, HPLC, liquid-liquid extraction or distribution, interactions such as hydrogen bridge bonds, ligand exchange and the formation of metal or charge transfer complexes are used to separate the enantiomers. In order to separate enantiomers by chromatographic methods generally optically active adsorbence are used, while chiral stationary or mobile phases are used. A known example is the racemate cleaving of Tröger's base using lactose.
Enantiomer separation is of great importance particularly in the pharmaceutical field in which specific compounds are of interest, i.e. only those enantiomeric forms which have the desired pharmacological and toxicological effects. For example, the enantiomers of the 5-hydroxy-3-ketoesters or the 5,6-dihydro-4-hydroxy-2-pyrones which can be obtained from them are important structural elements in a number of pharmaceutically active compounds, the class of the 5,6-dihydro-4-hydroxy-2-pyrone-sulphonamides being particularly important as they are used as non-peptidic HIV protease inhibitors. A particularly effective example of a potent HIV protease inhibitor of this category which is orally bioavailable is the compound Tipranavir (PNU-140690), which has the following structure:

This and other structurally similar compounds are known from the prior art (cf. for example J. Med. Chem. 1998, 41, 3467–3476).
A key step in the synthesis of the above-mentioned and structurally similar compounds is the reaction of 5,6-dihydro-4-hydroxy-2-pyrones 1 with suitably substituted carbonyl compounds 2 to form the condensation products 3, as illustrated in the following Diagram 1:

The meaning of the different groups R1 and R2 being given in the description of the present invention. The groups R and R′ are variable and are determined by the substitution pattern for the target compounds in question as are apparent from the prior art.
One method of preparing or obtaining enantiomers of the optically active dihydropyrones is already known from the prior art. Thus, WO 02/068404 A1 describes a process of this kind in which first of all suitably substituted carbonyl compounds are reacted with an acetoacetic acid derivative in the presence of organic or inorganic bases to form a racemic mixture of 5,6-dihydro-4-hydroxy-2-pyrones. The racemic mixture obtained is then converted with a chiral aminoalcohol into the salts, while depending on the choice of the aminoalcohol the desired salts of the R- or S- configuration can be crystallised out and the remaining enantiomer remains in solution.
The invention is thus based on the problem of providing a process, as a further development of the prior art, which allows 1 (B) to be synthesised in high yields, with a high enantiomeric purity, with the least possible technical expenditure and a high space/time yield. This process should also be suitable for use on a larger industrial scale, i.e. it should be cheap and therefore economical to carry out. Moreover, the compounds 1 (B) provided according to the invention, which are of central importance in the synthesis of the above-mentioned pharmaceutically active compounds, should not lose the chiral information contained in the starting compounds in the course of the subsequent reaction or reactions but this information should be retained in any case so that the desired properties are achieved.